1-Substituted-2-aminobenzimidazole compounds inhibit the growth of certain viruses, such as rhinoviruses, polio (types I, II, III), Coxsackie (A9, A21, B5), echo virus (strains 1, 2, 3, 4), and Mengo virus. Certain sulfonylbenzimidazole antiviral compounds are disclosed in U.S. Pat. Nos. 4,118,742 and 4,174,454.
The preparation of these compounds in the above references follows the methods disclosed in U.S. Pat. Nos. 4,018,790 and 4,118,573. Both of these patents reveal the reaction of a benzimidazole compound and a sulfonyl chloride compound in an organic solvent, preferably using a hazardous base such as sodium hydride. The patents do not divulge the use of an aqueous solution as in the presently claimed process.
Certain thiazolinyl or thiazinyl benzimidazole compounds are disclosed in U.S. Pat. Nos. 4,008,243 and 4,150,028 as antiviral agents. However, the process disclosed for their preparation is different from the novel claimed process of this application.
In Chemical Reviews, 48, 397-541 (1951), John B. Wright reports that the imidazole ring of benzimidazole compounds is cleaved by an acid halide and water to form the diamine compound.
Charles Price and Robert Reitsema in "Some Sulfonamide Derivatives of 2-Aminobenzimidazole", Journal of Organic Chemistry, 12, 269-274 (1947) describe the formation of 2-aminobenzimidazole-3-nitrobenzesulfonate by treating 1-(3-nitrophenylsulfonyl)-2-aminobenzimidazole with sodium hydroxide and acetic acid.
Copending application, Ser. No. 366,759, filed of even date herewith, claims a process for removing a sulfonyl substituent from the 1-position of 2-amino-5-substituted-benzimidazole to form the corresponding tautomeric benzimidazole. Another copending application, Ser. No. 366,760, also filed of even date herewith, describes a series of 5- and 6-substituted-ethylenicbenzimidazole compounds.